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  • Frontiers Media SA  (1,849)
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  • 1
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-10-20)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-20)
    Abstract: CT053PTSA is a novel tyrosine kinase inhibitor that targets MET, AXL, VEGFR2, FLT3 and MERTK. Here, we present preclinical data about CT053PTSA, and we conducted the first-in-human (FIH) study to evaluate the use of CT053PTSA in adult patients with pretreated advanced solid tumors. Methods The selectivity and antitumor activity of CT053PTSA were assessed in cell lines in vitro through kinase and cellular screening panels and in cell line-derived tumor xenograft (CDX) and patient-derived xenograft (PDX) models in vivo . The FIH, phase I, single-center, single-arm, dose escalation (3 + 3 design) study was conducted, patients received at least one dose of CT053PTSA (15 mg QD, 30 mg QD, 60 mg QD, 100 mg QD, and 150 mg QD). The primary objectives were to assess safety and tolerability, to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended dose of CT053PTSA for further study. Secondary objectives included pharmacokinetics, antitumor activity. Results CT053 (free-base form of CT053PTSA) inhibited MET, AXL, VEGFR2, FLT3 and MERTK phosphorylation and suppressed tumor cell angiogenesis by blocking VEGF and HGF, respectively, in vitro . Moreover, cell lines with high MET expression exhibited strong sensitivity to CT053, and CT053 blocked the MET and AXL signaling pathways. In an in vivo study, CT053 significantly inhibited tumor growth in CDX and PDX models. Twenty eligible patients were enrolled in the FIH phase I trial. The most common treatment-related adverse events were transaminase elevation (65%), leukopenia (45%) and neutropenia (35%). DLTs occurred in 3 patients, 1/6 in the 100 mg group and 2/4 in the 150 mg group, so the MTD was set to 100 mg. CT053PTSA was rapidly absorbed after the oral administration of a single dose, and the C max and AUC increased proportionally as the dose increased. A total of 17 patients in this trial underwent tumor imaging evaluation, and 29.4% had stable disease. Conclusions CT053PTSA has potent antitumor and antiangiogenic activity in preclinical models. In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1024755
    DOI: 10.3389/fimmu.2022.1024755.s001
    DOI: 10.3389/fimmu.2022.1024755.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
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    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-8-30)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-30)
    Abstract: In adult diffuse glioma, preoperative detection of isocitrate dehydrogenase ( IDH ) status helps clinicians develop surgical strategies and evaluate patient prognosis. Here, we aim to identify an optimal machine-learning model for prediction of IDH genotyping by combining deep-learning (DL) signatures and conventional radiomics (CR) features as model predictors. Methods In this study, a total of 486 patients with adult diffuse gliomas were retrospectively collected from our medical center (n=268) and the public database (TCGA, n=218). All included patients were randomly divided into the training and validation sets by using nested 10-fold cross-validation. A total of 6,736 CR features were extracted from four MRI modalities in each patient, namely T1WI, T1CE, T2WI, and FLAIR. The LASSO algorithm was performed for CR feature selection. In each MRI modality, we applied a CNN+LSTM–based neural network to extract DL features and integrate these features into a DL signature after the fully connected layer with sigmoid activation. Eight classic machine-learning models were analyzed and compared in terms of their prediction performance and stability in IDH genotyping by combining the LASSO–selected CR features and integrated DL signatures as model predictors. In the validation sets, the prediction performance was evaluated by using accuracy and the area under the curve (AUC) of the receiver operating characteristics, while the model stability was analyzed by using the relative standard deviation of the AUC (RSD AUC ). Subgroup analyses of DL signatures and CR features were also individually conducted to explore their independent prediction values. Results Logistic regression (LR) achieved favorable prediction performance (AUC: 0.920 ± 0.043, accuracy: 0.843 ± 0.044), whereas support vector machine with the linear kernel (l-SVM) displayed low prediction performance (AUC: 0.812 ± 0.052, accuracy: 0.821 ± 0.050). With regard to stability, LR also showed high robustness against data perturbation (RSD AUC : 4.7%). Subgroup analyses showed that DL signatures outperformed CR features (DL, AUC: 0.915 ± 0.054, accuracy: 0.835 ± 0.061, RSD AUC : 5.9%; CR, AUC: 0.830 ± 0.066, accuracy: 0.771 ± 0.051, RSD AUC : 8.0%), while DL and DL+CR achieved similar prediction results. Conclusion In IDH genotyping, LR is a promising machine-learning classification model. Compared with CR features, DL signatures exhibit markedly superior prediction values and discriminative capability.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1143688
    DOI: 10.3389/fonc.2023.1143688.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-10-28)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-28)
    Abstract: Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1049812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Presentation_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Aging Neuroscience Vol. 14 ( 2022-6-30)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-6-30)
    Abstract: To develop a prognostic prediction model of endovascular treatment (EVT) for acute ischemic stroke (AIS) induced by large-vessel occlusion (LVO), this study applied machine learning classification model light gradient boosting machine (LightGBM) to construct a unique prediction model. Methods A total of 973 patients were enrolled, primary outcome was assessed with modified Rankin scale (mRS) at 90 days, and favorable outcome was defined using mRS 0–2 scores. Besides, LightGBM algorithm and logistic regression (LR) were used to construct a prediction model. Then, a prediction scale was further established and verified by both internal data and other external data. Results A total of 20 presurgical variables were analyzed using LR and LightGBM. The results of LightGBM algorithm indicated that the accuracy and precision of the prediction model were 73.77 and 73.16%, respectively. The area under the curve (AUC) was 0.824. Furthermore, the top 5 variables suggesting unfavorable outcomes were namely admitting blood glucose levels, age, onset to EVT time, onset to hospital time, and National Institutes of Health Stroke Scale (NIHSS) scores (importance = 130.9, 102.6, 96.5, 89.5 and 84.4, respectively). According to AUC, we established the key cutoff points and constructed prediction scale based on their respective weightings. Then, the established prediction scale was verified in raw and external data and the sensitivity was 80.4 and 83.5%, respectively. Finally, scores & gt;3 demonstrated better accuracy in predicting unfavorable outcomes. Conclusion Presurgical prediction scale is feasible and accurate in identifying unfavorable outcomes of AIS after EVT.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2022.942285
    DOI: 10.3389/fnagi.2022.942285.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 5
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    DataSheet1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-8-28)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-8-28)
    Abstract: Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p & lt; 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness ( p & lt; 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: ( https://www.chictr.org.cn/ ), identifier (ChiCTR1900027175).
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1176980
    DOI: 10.3389/fphar.2023.1176980.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 6
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    Prevalence and factors associated with visual impairment in middle-aged and older Chinese population
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-11-28)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-28)
    Abstract: This study aimed to estimate the prevalence of visual impairment and to identify the factors associated with it in China. Methods Data for this cross-sectional study were retrieved from the China Health and Retirement Longitudinal Study (CHARLS) for a total of 16,480 subjects who completed the questionnaire between June 2011 and March 2012. The prevalence of visual impairment was estimated considering the complex survey design and response rate. Associated factors were identified using the weighted logistic regression analysis. Results The overall prevalence of visual impairment among middle-aged and older Chinese adults was 6.22%. Regionally, Qinghai and Gansu provinces showed the highest prevalence of visual impairment, whereas Shanghai showed the lowest prevalence of visual impairment in China. Older age (OR = 1.888; 95% CI: 1.537–2.467) was correlated with a higher likelihood of visual impairment, whereas a non-alcohol intake (OR = 0.072; 95% CI: 0.018–0.246) was correlated with a lower likelihood of visual impairment. Hypertension (OR = 1.299; 95% CI: 1.189–1.467), diabetes (OR = 2.000; 95% CI: 1.163–3.765), lung diseases (OR = 1.795; 95% CI: 1.067–3.019), liver diseases (OR = 1.270; 95% CI: 1.221–2.876), stroke (OR = 1.135; 95% CI: 1.107–3.528), and heart disease (OR = 1.350; 95% CI: 1.104–1.708) were significantly associated with visual impairment. Conclusion Geographical variations in the prevalence of visual impairment in China were defined, indicating that such variations do exist in China. Age, alcohol intake, hypertension, diabetes, lung diseases, liver diseases, stroke, and heart disease were factors associated with visual impairment.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.962729
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 7
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    Genome-wide analysis and expression profiling under heat and drought treatments of HSP70 gene family in soybean (Glycine max L.)
    Frontiers Media SA ; 2015
    In:  Frontiers in Plant Science Vol. 6 ( 2015-09-25)
    Details
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 6 ( 2015-09-25)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    URL: Article
    DOI: 10.3389/fpls.2015.00773
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2015
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 8
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    PF-06409577 Activates AMPK Signaling and Inhibits Osteosarcoma Cell Growth
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-14)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-14)
    Abstract: Osteosarcoma (OS) is a common primary bone malignancy. We here investigated the potential activity of PF-06409577, a novel, potent, and direct activator of AMP-activated protein kinase (AMPK), against human OS cells. In established (U2OS, MG-63, and SaOs-2 lines) and primary human OS cells, PF-06409577 inhibited cell viability and proliferation, while inducing cell apoptosis and cell cycle arrest. PF-06409577 induced AMPK activation, mTORC1 inhibition, autophagy induction, and downregulation of multiple receptor tyrosine kinase inOS cells. AMPK inactivation by AMPK α 1 shRNA, CRISPR/Cas9 knockout, or dominant negative mutation (T172A) was able to abolish PF-06409577-induced activity in OS cells. In vivo , PF-06409577 oral administration at well-tolerated doses potently inhibited growth of U2OS cells and primary human OS cells in severe combined immunodeficient mice. AMPK activation, mTORC1 inhibition, autophagy induction, as well as RTK degradation and apoptosis activation were detected in PF-06409577-treated xenografts. In conclusion, activation of AMPK by PF-06409577 inhibits OS cell growth.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.659181
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 9
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-3-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-3-4)
    Abstract: Largemouth bass iridovirus (LMBV) can cause high mortality and lead to heavy economic loss in the cultivation of largemouth bass, but there was no effective treatment. Here, the present study constructed a recombinant Pichia pastoris expressing LMBV major capsid protein ( MCPD ). The recombinant GS115-pW317- MCPD was then used to immunize largemouth bass via oral administration, and mucosal immune response mediated by immunoglobulins (Igs) was measured after oral immunization. Serum antibody levels were measured by ELISA, neutralizing antibody titers were determined by serum neutralization test (SNT), antigen presentation-related gene expressions were detected by RT-PCR, and the histopathological characteristics of immunized fish were assessed after challenging with 0.1 ml 10 7.19 TCID 50 /ml LMBV. The relative percentage survival (RPS) was also determined. Our results showed that the serum antibody titers of immunized fish were significantly higher than that of control groups (P & lt; 0.05). IgT and IgM expressions in gut were increased significantly after vaccination with GS115-pW317- MCPD ; however, much stronger response in gut was observed as compared with gill. The expression levels of major histocompatibility complex ( MHC ) II, CD 8, and T-cell receptor ( TCR ) were significantly elevated in GS115-pW317- MCPD group (P & lt; 0.05), while CD 4 and MHC I transcription levels remained unchanged after oral immunization ( P & gt; 0.05). The RPS of fish orally immunized with 1.0 × 10 8 CFU/g GS115-pW317- MCPD was reached up to 41.6% after challenge with 0.1 ml 10 9.46 TCID 50 /ml LMBV. Moreover, orally immunizing with GS115-pW317- MCPD can relieve the pathological damage caused by LMBV. Therefore, GS115-pW317- MCPD showed a promising potential against LMBV.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.852300
    DOI: 10.3389/fimmu.2022.852300.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Functional Disability After Ischemic Stroke: A Community-Based Cross-Sectional Study in Shanghai, China
    Frontiers Media SA ; 2021
    In:  Frontiers in Neurology Vol. 12 ( 2021-8-26)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 12 ( 2021-8-26)
    Abstract: Objective: This study aimed to understand the demographics, functional disabilities, cognitive impairment, and depressive mood among stroke patients and to explore the correlation between functional disability and the other health conditions so as to provide some data for community rehabilitation among stroke patients. Methods: A cross-sectional study was conducted to investigate the functional status of ischemic stroke patients with stroke history between 1 month and 2 years by applying the modified Rankin Scale (mRS). Data were collected during October 2016 and January 2017 from 11 communities in two districts of Shanghai, China. We used face-to-face questionnaire interviews to collect information on sociodemographics, vascular risks associated with stroke, cognitive function [Mini-Mental State Examination (MMSE)] , and depression [Patient Health Questionnaire-9 (PHQ-9)]; and we applied SPSS 24.0 for data analysis. Results: In this study, 305 patients with ischemic stroke were finally recruited, including 189 (61.97%) men, with an average age of 67 years. According to the mRS score, ischemic stroke patients were divided into patients without symptoms (controls, mRS = 0), patients without obvious disability (mRS = 1), and patients with mild to severe disability (mRS = 2–5). Ischemic stroke patients with different mRS levels demonstrated significant differences in age, tobacco smoke exposure, previous stroke history, cognitive function, and depression status. Compared with patients without symptoms (mRS = 0), patients with mRS = 1 had a lower MMSE score [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26–0.90]; and patients with mRS = 2–5 had a lower MMSE score [OR = 0.16, 95% CI: 0.08–0.33] , had a higher PHQ-9 score [OR = 5.36, 95% CI: 2.19–13.11], and were more likely to have previous stroke history [OR = 2.18, 95% CI: 1.01–4.79] . Conclusion: Lower degrees of functional independence are related to cognitive impairment, as well as the previous stroke history and depression status.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2021.649088
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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